Natural cell-mediated cytotoxicity against mouse and rat tumor cells has been studied. Normal lymphocytes of many animals are cytotoxic for lymphomas, carcinomas and sarcomas. The natural effector cell lacks easily definable surface markers, but appears to have an Fc receptor and to be an early T cell. The natural cytotoxicity appears to play an important role in in vivo resistance to tumor growth. Lymphoproliferative responses to tumor associated antigens in mice and rats have been detected. These are inhibited by suppressor macrophages, found in increased amounts in tumor-bearing individuals. These cells also can inhibit growth of tumor cells. Lymphoproliferative responses were also markedly inhibited by rodent parvoviruses, frequent contaminants of transplantable tumors. Adoptive transfer of resistance to growth of the rat tumor (C58NT)D was mediated by T cells from immune rats, obtained 30-50 days after immunization. This correlated with the presence of cytotoxic memory cells and of cells responsive in mixed lymphocyte tumor interactions, but not with directly cytotoxic cells. Separable subpopulations of human peripheral blood T lymphocytes formed rosettes with sheep erythrocytes at 29 degrees C or only at 4 degrees C. Thymosin affected the properties of the cells.